This proposal is a continuation of our efforts to characterize, using molecular genetics, the class I gene family of the human major histocompatibility complex (MHC). In addition to maintaining the transplantation barrier between individuals, molecules encoded by the MHC have a central role in regulating the immune response. The class I loci constitute a multigene family whose hallmark is a high level of polymorphism. We will continue to focus our attention on the class I gene family of lymphoblastoid cell line (LCL) 721. LCL 721 was chosen because of the large number of HLA deletion mutants which have been derived from it by Dr. DeMars of the University of Wisconsin. These mutants have been used to map DNA fragments to the known HLA-A and -B alleles of LCL 721 (26). Two of these, HLA-A2 and -A1 will be cloned and sequenced as a beginning in understanding the molecular basis of HLA polymorphism. Our mapping studies have also identified class I-like sequences located telomeric to HLA-A2 (19), as an analogous position relative to the MHC as the murine QA-Tla genes. In order to ascertain the relationship between the human class I-like telomeric sequences and the murine Qa-Tla genes, we will obtain genomic clones of the telomeric segments. These will then be subjected to DNA sequencing and studies directed at determining if these sequences include expressed genes. An important aspect will be to determine the tissue distribution of any class I-like genes found to be expresses. Understanding the relationship to the murine Qa-Tla genes of the human class I-like DNA located telomerically to HLA should help to identify useful markers of human lymphocyte differentiation.